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Molecular and Cellular Biochemistry

, Volume 366, Issue 1–2, pp 269–275 | Cite as

Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue

  • Mohammad A. Mohammad
  • Ahmed A. Zeeneldin
  • Zakaria Y. Abd Elmageed
  • Ebtsam H. Khalil
  • Said M. E. Mahdy
  • Hayat M. Sharada
  • Sabry K. Sharawy
  • Abdel-Hady A. Abdel-WahabEmail author
Article

Abstract

Breast cancer (BC) is the most common neoplasm among women in most developed countries, including Egypt. Elevated levels of certain proteins in human BC are associated with unfavorable prognosis and progressive stages of the disease. The aim of our study was to evaluate the protein expression profile and prognostic significance of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), MMP-9 and membrane type 1-MMP (MT1-MMP) and their interaction in operable BC patients. The protein expression of COX-2, MMP-2 and MT1-MMP were evaluated by western blot technique, whereas enzymatic activity of MMP-2 and MMP-9 was determined by zymography in 47 breast cancer patients as well as normal adjacent tissues. Also, the correlation between these proteins and age, tumor size, LN stage, TNM stage, estrogen receptor, progesterone receptor, disease-free survival, and overall survival (OS) has been investigated. As compared to adjacent normal tissues, COX-2, MMP-2 and MT1-MMP were over-expressed in 43, 64, and 60 % of tumor tissues, respectively. In the same pattern, the activity of MMP-2 (62 %) and MMP-9 (45 %) was elevated in BC tissues. Multivariate analysis showed a positive correlation between the protein expression of COX-2, MMP-2, and MT1-MMP and the activity of MMP-2 and MMP-9 in BC patients. However, the enzymatic activity showed no correlation with clinicopathological features. This study confirms the preclinical evidence that COX-2 increased the expression of MT1-MMP, which in turn activates MMP-2. The lack of correlation with clinicopathological features, OS or disease-free survival ascertains the complexity of tumor progression and metastasis with many pro- and counter regulatory factors.

Keywords

Breast cancer Cox-2 MMPs MT1-MMP Western blot Zymography 

Notes

Acknowledgments

This work was supported by grant from National Cancer Institute (NCI-48019), Cairo University, Cairo, Egypt.

Conflict of interest

We declare that we have no conflict of interest for any of the authors including financial, personal or other relationships with other people or organization.

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Mohammad A. Mohammad
    • 1
  • Ahmed A. Zeeneldin
    • 2
  • Zakaria Y. Abd Elmageed
    • 3
  • Ebtsam H. Khalil
    • 4
  • Said M. E. Mahdy
    • 4
  • Hayat M. Sharada
    • 4
  • Sabry K. Sharawy
    • 1
  • Abdel-Hady A. Abdel-Wahab
    • 1
    Email author
  1. 1.Department of Cancer BiologyNational Cancer Institute, Cairo UniversityCairoEgypt
  2. 2.Department of Medical OncologyNational Cancer Institute, Cairo UniversityCairoEgypt
  3. 3.Department of Urology and OncologyTulane University Medical CenterNew OrleansUSA
  4. 4.Department of Chemistry, Faculty of ScienceHelwan UniversityHelwanEgypt

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